Carnosine, oxidative and carbonyl stress, antioxidants, and muscle fiber characteristics of quadriceps muscle of patients with COPD.

Oxidative/carbonyl stress is elevated in lower-limb muscles of patients with chronic obstructive pulmonary disease (COPD). Carnosine is a skeletal muscle antioxidant particularly present in fast-twitch fibers. The aims of the present study were to compare muscle carnosine, oxidative/carbonyl stress, antioxidants, and fiber characteristics between patients with COPD and healthy controls (HCs) and between patients after stratification for airflow limitation (mild/moderate vs. severe/very severe), as well as to investigate correlates of carnosine in patients with COPD. A vastus lateralis muscle biopsy was obtained from 40 patients with stable COPD and 20 age- and sex-matched HCs. Carnosine, oxidative/carbonyl stress, antioxidants, fiber characteristics, quadriceps strength and endurance (QE), V̇o2peak (incremental cycle test), and physical activity (PA) were determined. Patients with COPD had a similar carnosine concentration [4.16 mmol/kg wet weight (WW; SD = 1.93)] to HCs [4.64 mmol/kg WW (SD = 1.71)] and significantly higher percentage of fast-twitch fibers and lower QE, V̇o2peak, and PA versus HCs. Patients with severe/very severe COPD had a 31% lower carnosine concentration [3.24 mmol/kg WW (SD = 1.79); n = 15] versus patients with mild/moderate COPD [4.71 mmol/kg WW (SD = 1.83); n = 25; P = 0.02] and significantly lower V̇o2peak and PA versus patients with mild/moderate COPD. Carnosine correlated significantly with QE (rs = 0.427), V̇o2peak (rs = 0.334), PA (rs = 0.379), and lung function parameters in patients with COPD. In conclusion, despite having the highest proportion of fast-twitch fibers, patients with severe/very severe COPD displayed a 31% lower muscle carnosine concentration compared with patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.NEW & NOTEWORTHY Carnosine, particularly present in fast-twitch fibers, was investigated in the quadriceps of patients with chronic obstructive pulmonary disease (COPD). Carnosine concentration was similar between patients with COPD and healthy controls but was 31% lower in patients with severe/very severe COPD, despite their high proportion of fast-twitch fibers, versus patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.

CORP: quantification of human skeletal muscle carnosine concentration by proton magnetic resonance spectroscopy.

Noninvasive techniques to quantify metabolites in skeletal muscle provide unique insight into human physiology and enable the translation of research into practice. Proton magnetic resonance spectroscopy (1H-MRS) permits the assessment of several abundant muscle metabolites in vivo, including carnosine, a dipeptide composed of the amino acids histidine and beta-alanine. Muscle carnosine loading, accomplished by chronic oral beta-alanine supplementation, improves muscle function and exercise capacity and has pathophysiological relevance in multiple diseases. Moreover, the marked difference in carnosine content between fast-twitch and slow-twitch muscle fibers has rendered carnosine an attractive candidate to estimate human muscle fiber type composition. However, the quantification of carnosine with 1H-MRS requires technical expertise to obtain accurate and reproducible data. In this review, we describe the technical and physiological factors that impact the detection, analysis, and quantification of carnosine in muscle with 1H-MRS. We discuss potential sources of error during the acquisition and preprocessing of the 1H-MRS spectra and present best practices to enable the accurate, reliable, and reproducible application of this technique.

Acute preexercise supplementation of combined carnosine and anserine enhances initial maximal power of Wingate tests in humans.

Classic in vitro experiments (Severin's phenomenon) demonstrated that acute carnosine supplementation may potentiate muscle contractility. However, upon oral ingestion, carnosine is readily degraded in human plasma by the highly active serum carnosinase-1 (CN1). We developed a novel strategy to circumvent CN1 by preexercise ingestion of combined carnosine (CARN) and anserine (ANS), the methylated analog with similar biochemical properties but more resistant to CN1. First, in vitro hydrolysis was tested by adding carnosine and anserine to human plasma, alone or in combination. Second, five subjects were supplemented with 25 mg/kg anserine or 25 mg/kg of each anserine and carnosine to test in vivo bioavailability. Third, two double-blind, placebo-controlled, crossover studies investigated the effect of preexercise ANS + CARN (20 mg/kg body wt of each) supplementation on performance during a single all-out Wingate test following 6-min high-intensity cycling (study A) or three repeated Wingate tests (study B). In vitro experiments demonstrated slower degradation of anserine versus carnosine, which was further slowed by simultaneously adding carnosine. In vivo bioavailability of plasma anserine was more prominent [2.5-fold increased area under the curve (AUC)] when ANS + CARN versus ANS was ingested. Study A showed significantly higher (+6% ± 11%; P = 0.04) power in the first 5 s of the Wingate test following ANS + CARN (12.8 ± 2.4 W/kg) versus placebo (12.1 ± 2.2 W/kg). Study B demonstrated increased peak power (+3%) throughout three consecutive Wingate tests (ANS + CARN 10.5 ± 0.6 W/kg vs. placebo 10.2 ± 9.9 W/kg). These experiments reveal a novel acute nutritional method to effectively raise plasma anserine and carnosine by high-dose combined supplementation. This approach led to improved initial cycling power, revealing a new nutritional strategy to increase exercise performance.NEW & NOTEWORTHY Current results reveal that carnosine and anserine competitively bind to the highly active carnosinase enzyme in human plasma. Acute combined carnosine and anserine supplementation is therefore described as novel strategy to raise plasma anserine and carnosine. We report that indices of maximal exercise/muscle power during the initial stage of a Wingate test were significantly improved by preexercise 20-25mg/kg body wt anserine and carnosine supplementation, pointing toward a novel acute nutritional strategy to improve high-intensity exercise performance.

Cyclic movement frequency is associated with muscle typology in athletes.

There is a continuing research interest in the muscle fiber type composition (MFTC) of athletes. Recently, muscle carnosine quantification by proton magnetic resonance spectroscopy (1 H-MRS) was developed as a new non-invasive method to estimate MFTC. This cross-sectional study aims to better understand estimated MFTC in relation to (a) different disciplines within one sport; (b) cyclic sport exercise characteristics; (c) within-athlete variability; and (d) athlete level. A total of 111 elite athletes (74 runners, 7 triathletes, 11 swimmers, 14 cyclists and 5 kayakers) and 188 controls were recruited to measure muscle carnosine in gastrocnemius and deltoid muscle by 1 H-MRS. Within sport disciplines, athletes were divided into subgroups (sprint-, intermediate-, and endurance-type). The controls were used as reference population to allow expression of the athletes' data as Z-scores. Within different sports, endurance-type athletes systematically showed the lowest Z-score compared to sprint-type athletes, with intermediate-type athletes always situated in between. Across the different sports disciplines, carnosine content showed the strongest significant correlation with cyclic movement frequency (R = 0.86, P = 0.001). Both within and between different cyclic sports, estimated MFTC was divergent between sprint- and endurance-type athletes. Cyclic movement frequency, rather than exercise duration came out as the most determining factor for the optimal estimated MFTC in elite athletes.

Discriminant musculo-skeletal leg characteristics between sprint and endurance elite Caucasian runners.

Excellence in either sprinting or endurance running requires specific musculo-skeletal characteristics of the legs. This study aims to investigate the morphology of the leg of sprinters and endurance runners of Caucasian ethnicity. Eight male sprinters and 11 male endurance runners volunteered to participate in this cross-sectional study. They underwent magnetic resonance imaging and after data collection, digital reconstruction was done to calculate muscle volumes and bone lengths. Sprinters have a higher total upper leg volume compared to endurance runners (7340 vs 6265 cm3 ). Specifically, the rectus femoris, vastus lateralis, and hamstrings showed significantly higher muscle volumes in the sprint group. For the lower leg, only a higher muscle volume was found in the gastrocnemius lateralis for the sprinters. No differences were found in muscle volume distribution, center of mass in the different muscles, or relative bone lengths. There was a significant positive correlation between ratio hamstrings/quadriceps volume and best running performance in the sprint group. Sprinters and endurance runners of Caucasian ethnicity showed the greatest distinctions in muscle volumes, rather than in muscle distributions or skeletal measures. Sprinters show higher volumes in mainly the proximal and lateral leg muscles than endurance runners.

Exoskeleton plantarflexion assistance for elderly.

Elderly are confronted with reduced physical capabilities and increased metabolic energy cost of walking. Exoskeletons that assist walking have the potential to restore walking capacity by reducing the metabolic cost of walking. However, it is unclear if current exoskeletons can reduce energy cost in elderly. Our goal was to study the effect of an exoskeleton that assists plantarflexion during push-off on the metabolic energy cost of walking in physically active and healthy elderly. Seven elderly (age 69.3±3.5y) walked on treadmill (1.11ms2) with normal shoes and with the exoskeleton both powered (with assistance) and powered-off (without assistance). After 20min of habituation on a prior day and 5min on the test day, subjects were able to walk with the exoskeleton and assistance of the exoskeleton resulted in a reduction in metabolic cost of 12% versus walking with the exoskeleton powered-off. Walking with the exoskeleton was perceived less fatiguing for the muscles compared to normal walking. Assistance resulted in a statistically nonsignificant reduction in metabolic cost of 4% versus walking with normal shoes, likely due to the penalty of wearing the exoskeleton powered-off. Also, exoskeleton mechanical power was relatively low compared to previously identified optimal assistance magnitude in young adults. Future exoskeleton research should focus on further optimizing exoskeleton assistance for specific populations and on considerate integration of exoskeletons in rehabilitation or in daily life. As such, exoskeletons should allow people to walk longer or faster than without assistance and could result in an increase in physical activity and resulting health benefits.

ß-Alanine does not act through branched-chain amino acid catabolism in carp, a species with low muscular carnosine storage.

This study was executed to investigate the effect of dietary ß-alanine (BA) on amino acid (AA) metabolism and voluntary feed intake in carp (Cyprinus carpio) at mildly elevated temperature to exert AA catabolism. Twenty-four fish in 12 aquaria were randomly assigned to either a control diet or the same diet with 500 mg BA/kg. A 14-day period at an ideal temperature (23 °C) was followed by 15 days at chronic mildly elevated temperature (27 °C). After the 15 days, all fish were euthanised for muscle analysis on histidine-containing dipeptides (HCD), whole blood on free AA and carnitine esters. The carnosine and anserine analysis indicated that all analyses were below the detection limit of 5 µmol/L, confirming that carp belongs to a species that does not store HCD. The increases in free AA concentrations due to BA supplementation failed to reach the level of significance. The effects of dietary BA on selected whole blood carnitine esters and their ratios were also not significant. The supplementation of BA tended to increase body weight gain (P = 0.081) and feed intake (P = 0.092). The lack of differences in the selected nutrient metabolites in combination with tendencies of improved growth performance warrants further investigation to unravel the mechanism of BA affecting feed intake. This first trial on the effect of BA supplementation on AA catabolism showed that its metabolic effect in carp at chronic mildly elevated temperature was very limited. Further studies need to evaluate which conditions are able to exert an effect of BA on AA metabolism.

Uphill walking with a simple exoskeleton: plantarflexion assistance leads to proximal adaptations.

While level walking with a pneumatic ankle-foot exoskeleton is studied extensively, less is known on uphill walking. The goals of this study were to get a better understanding of the biomechanical adaptations and the influence of actuation timing on metabolic cost during uphill walking with a plantarflexion assisting exoskeleton. Seven female subjects walked on a treadmill with 15% inclination at 1.36 ms(-1) in five conditions (4 min): one condition with an unpowered exoskeleton and four with a powered exoskeleton with onset of pneumatic muscle actuation at 19, 26, 34 and 41% of stride. During uphill walking the metabolic cost was more than 10% lower for all powered conditions compared to the unpowered condition. When actuation onset was in between 26 and 34% of the stride, metabolic cost was suggested to be minimal. While it was expected that exoskeleton assistance would reduce muscular activity of the plantarflexors during push-off, subjects used the additional power to raise the body centre of mass in the beginning of each step to a higher point compared to unpowered walking. This reduced the muscular activity in the m. vastus lateralis and the m. biceps femoris as less effort was necessary to reach the highest body centre of mass position in the single support phase. In conclusion, subjects can use plantarflexion assistance during the push-off to reduce muscular activity in more proximal joints in order to minimize energy cost during uphill locomotion. Kinetic data seem necessary to fully understand this mechanism, which highlights the complexity of human-exoskeleton interaction.

Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice.

PURPOSE: The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model. METHODS: We examined the effects of Orx either with or without testosterone (T) or estradiol (E2) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice. RESULTS: Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E2 administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E2, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx. CONCLUSIONS: The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy.

Muscle carnosine loading by beta-alanine supplementation is more pronounced in trained vs. untrained muscles.

Carnosine occurs in high concentrations in human skeletal muscle and assists working capacity during high-intensity exercise. Chronic beta-alanine (BA) supplementation has consistently been shown to augment muscle carnosine concentration, but the effect of training on the carnosine loading efficiency is poorly understood. The aim of the present study was to compare muscle carnosine loading between trained and untrained arm and leg muscles. In a first study (n = 17), reliability of carnosine quantification by proton magnetic resonance spectroscopy ((1)H-MRS) was evaluated in deltoid and triceps brachii muscles. In a second study, participants (n = 35; 10 nonathletes, 10 cyclists, 10 swimmers, and 5 kayakers) were supplemented with 6.4 g/day of slow-release BA for 23 days. Carnosine content was evaluated in soleus, gastrocnemius medialis, and deltoid muscles by (1)H-MRS. All the results are reported as arbitrary units. In the nonathletes, BA supplementation increased carnosine content by 47% in the arm and 33% in the leg muscles (not significant). In kayakers, the increase was more pronounced in arm (deltoid) vs. leg (soleus + gastrocnemius) muscles (0.089 vs. 0.049), whereas the reverse pattern was observed in cyclists (0.065 vs. 0.084). Swimmers had significantly higher increase in carnosine in both deltoid (0.107 vs. 0.065) and gastrocnemius muscle (0.082 vs. 0.051) compared with nonathletes. We showed that 1) carnosine content can be reliably measured by (1)H-MRS in deltoid muscle, 2) carnosine loading is equally effective in arm vs. leg muscles of nonathletes, and 3) carnosine loading is more pronounced in trained vs. untrained muscles.

Adaptation to walking with an exoskeleton that assists ankle extension.

The goal of this study was to investigate adaptation to walking with bilateral ankle-foot exoskeletons with kinematic control that assisted ankle extension during push-off. We hypothesized that subjects would show a neuromotor and metabolic adaptation during a 24min walking trial with a powered exoskeleton. Nine female subjects walked on a treadmill at 1.36±0.04ms(-1) during 24min with a powered exoskeleton and 4min with an unpowered exoskeleton. Subjects showed a metabolic adaptation after 18.5±5.0min, followed by an adapted period. Metabolic cost, electromyography and kinematics were compared between the unpowered condition, the beginning of the adaptation and the adapted period. In the beginning of the adaptation (4min), a reduction in metabolic cost of 9% was found compared to the unpowered condition. This reduction was accompanied by reduced muscular activity in the plantarflexor muscles, as the powered exoskeleton delivered part of the necessary ankle extension moment. During the adaptation this metabolic reduction further increased to 16%, notwithstanding a constant exoskeleton assistance. This increased reduction is the result of a neuromotor adaptation in which subjects adapt to walking with the exoskeleton, thereby reducing muscular activity in all leg muscles. Because of the fast adaptation and the significant reductions in metabolic cost we want to highlight the potential of an ankle-foot exoskeleton with kinematic control that assists ankle extension during push-off.

Mouth rinse but not ingestion of a carbohydrate solution improves 1-h cycle time trial performance.

The aim of the present study was to further explore the influence of ingestion and mouth rinse with a carbohydrate-electrolyte solution (CES) on the performance during a approximately 1 h high-intensity time trial on trained subjects. Subjects rinsed around the mouth or ingested a 6% isotonic CES or placebo (14 mL/kg body weight) before and throughout a time trial in which they had to accomplish a set amount of work (975+/-85 kJ) as quickly as possible. In the mouth rinse conditions, time to complete the test was shorter (P=0.02) with CES (61.7+/-5.1 min) than with placebo (64.1+/-6.5 min), whereas in the ingestion conditions, there was no difference between placebo (62.5+/-6.9 min) and CES (63.2+/-6.9 min). Although power output and lactate concentration during exercise were significantly higher when subjects rinsed their mouth with CES compared with placebo, the rating of perceived exertion values did not differ. Blood glucose concentration increased after ingestion of but not after mouth rinse with CES. The interesting finding of the present study is that rinsing the mouth with but not ingestion of CES resulted in improved performance.

Effect of training in the fasted state on metabolic responses during exercise with carbohydrate intake.

Skeletal muscle gene response to exercise depends on nutritional status during and after exercise, but it is unknown whether muscle adaptations to endurance training are affected by nutritional status during training sessions. Therefore, this study investigated the effect of an endurance training program (6 wk, 3 day/wk, 1-2 h, 75% of peak Vo(2)) in moderately active males. They trained in the fasted (F; n = 10) or carbohydrate-fed state (CHO; n = 10) while receiving a standardized diet [65 percent of total energy intake (En) from carbohydrates, 20%En fat, 15%En protein]. Before and after the training period, substrate use during a 2-h exercise bout was determined. During these experimental sessions, all subjects were in a fed condition and received extra carbohydrates (1 g.kg body wt(-1) .h(-1)). Peak Vo(2) (+7%), succinate dehydrogenase activity, GLUT4, and hexokinase II content were similarly increased between F and CHO. Fatty acid binding protein (FABPm) content increased significantly in F (P = 0.007). Intramyocellular triglyceride content (IMCL) remained unchanged in both groups. After training, pre-exercise glycogen content was higher in CHO (545 +/- 19 mmol/kg dry wt; P = 0.02), but not in F (434 +/- 32 mmol/kg dry wt; P = 0.23). For a given initial glycogen content, F blunted exercise-induced glycogen breakdown when compared with CHO (P = 0.04). Neither IMCL breakdown (P = 0.23) nor fat oxidation rates during exercise were altered by training. Thus short-term training elicits similar adaptations in peak Vo(2) whether carried out in the fasted or carbohydrate-fed state. Although there was a decrease in exercise-induced glycogen breakdown and an increase in proteins involved in fat handling after fasting training, fat oxidation during exercise with carbohydrate intake was not changed.

Fiber type-specific muscle glycogen sparing due to carbohydrate intake before and during exercise.

The effect of carbohydrate intake before and during exercise on muscle glycogen content was investigated. According to a randomized crossover study design, eight young healthy volunteers (n = 8) participated in two experimental sessions with an interval of 3 wk. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% maximal oxygen uptake). On one occasion (CHO), they received carbohydrates before ( approximately 150 g) and during (1 g.kg body weight(-1).h(-1)) exercise. On the other occasion they exercised after an overnight fast (F). Fiber type-specific relative glycogen content was determined by periodic acid Schiff staining combined with immunofluorescence in needle biopsies from the vastus lateralis muscle before and immediately after exercise. Preexercise glycogen content was higher in type IIa fibers [9.1 +/- 1 x 10(-2) optical density (OD)/microm(2)] than in type I fibers (8.0 +/- 1 x 10(-2) OD/microm(2); P < 0.0001). Type IIa fiber glycogen content decreased during F from 9.6 +/- 1 x 10(-2) OD/microm(2) to 4.5 +/- 1 x 10(-2) OD/microm(2) (P = 0.001), but it did not significantly change during CHO (P = 0.29). Conversely, in type I fibers during CHO and F the exercise bout decreased glycogen content to the same degree. We conclude that the combination of carbohydrate intake both before and during moderate- to high-intensity endurance exercise results in glycogen sparing in type IIa muscle fibers.

Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans.

The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% ), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before ( approximately 150 g) and during (1 g (kg bw)(-1) h(-1)) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 +/- 2% to 6 +/- 2% (P = 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 +/- 2% to 10 +/- 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise-induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 +/- 7.8 mmol kg(-1) h(-1)), mean rate of postexercise muscle glycogen resynthesis was 3-fold greater in F (32.9 +/- 2.7 mmol kg(-1) h(-1), P = 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 microU ml(-1)) than in CHO (+14.63 microU ml(-1), P = 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state. Furthermore, facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state.

Treadmill exercise negatively affects visual contribution to static postural stability.

This study was undertaken to explore the nature of impaired postural stability following physical exercise. Nine healthy subjects (aged 24 +/- 3 years) were subjected to 30 min of treadmill walking or running on two separate occasions. Walking and running speeds (1.9 to 2.2 m/s) were chosen to induce equal energy expenditure. During treadmill exercise, kinematic analysis of head movement was performed. Prior to and immediately following exercise, postural sway was evaluated as mean velocity of centre of pressure (VCOP), measured on a force plate during 30 s quiet stance with eyes open or eyes closed. The results indicate that exercise increased two-dimensional postural sway by 9 - 19 % in eyes open, but not in the eyes closed condition. The deteriorating effect of exercise was both evident in the sagittal and in the frontal plane, although the effect on the former was slightly more transient. Post-exercise sway values were significantly higher after running than after walking. Kinematic analysis of head movement confirmed larger vertical displacement and acceleration pattern in running compared to walking. It is concluded that exercise of moderate intensity deteriorates visual contribution to postural stability. The effect is evident as an initial destabilisation in the sagittal direction and a less transient loss of latero-lateral stability. Running tends to disturb postural stability more than walking, possibly due to more excessive head movement and disturbance of vestibular and visual information centres.

Glucose, exercise and insulin: emerging concepts.

Physical exercise induces a rapid increase in the rate of glucose uptake in the contracting skeletal muscles. The enhanced membrane glucose transport capacity is caused by a recruitment of glucose transporters (GLUT4) to the sarcolemma and t-tubules. This review summarises the recent progress in the understanding of signals that trigger GLUT4 translocation in contracting muscle. The possible involvement of calcium, protein kinase C (PKC), nitric oxide (NO), glycogen and AMP-activated protein kinase (AMPK) are discussed. Furthermore, the possible mechanisms behind the well-described improvement of insulin action on glucose uptake and glycogen synthase activity in the post-exercise period is discussed. It is concluded that both during and following muscle contractions, glycogen emerges as an important modulator of signalling events in glucose metabolism.

Glycogen synthase localization and activity in rat skeletal muscle is strongly dependent on glycogen content.

1. The influence of muscle glycogen content on glycogen synthase (GS) localization and GS activity was investigated in skeletal muscle from male Wistar rats. 2. Two groups of rats were obtained, preconditioned with a combination of exercise and diet to obtain either high (HG) or low (LG) muscle glycogen content. The cellular distribution of GS was studied using subcellular fractionation and confocal microscopy of immunostained single muscle fibres. Stimulation of GS activity in HG and LG muscle was obtained with insulin or contractions in the perfused rat hindlimb model. 3. We demonstrate that GS translocates from a glycogen-enriched membrane fraction to a cytoskeleton fraction when glycogen levels are decreased. Confocal microscopy supports the biochemical observations that the subcellular localization of GS is influenced by muscle glycogen content. GS was not found in the nucleus. 4. Investigation of the effect of glycogen content on GS activity in basal and insulin- and contraction-stimulated muscle shows that glycogen has a strong inhibitory effect on GS activity. Our data demonstrate that glycogen is a more potent regulator of glycogen synthase activity than insulin. Furthermore we show that the contraction-induced increase in GS activity is merely a result of a decrease in muscle glycogen content. 5. In conclusion, the present study shows that GS localization is influenced by muscle glycogen content and that not only basal but also insulin- and contraction-stimulated GS activity is strongly regulated by glycogen content in skeletal muscle.

Creatine supplementation: exploring the role of the creatine kinase/phosphocreatine system in human muscle.

The effect of oral creatine supplementation on high-intensity exercise performance has been extensively studied over the past ten years and its ergogenic potential in young healthy subjects is now well documented. Recently, research has shifted from performance evaluation towards elucidating the mechanisms underlying enhanced muscle functional capacity after creatine supplementation. In this review, we attempt to summarise recent advances in the understanding of potential mechanisms of action of creatine supplementation at the level of skeletal muscle cells. By increasing intracellular creatine content, oral creatine ingestion conceivably stimulates operation of the creatine kinase (CK)/phosphocreatine (PCr) system, which in turn facilitates muscle relaxation. Furthermore, evidence is accumulating to suggest that creatine supplementation can beneficially impact on muscle protein and glycogen synthesis. Thus, muscle hypertrophy and glycogen supercompensation are candidate factors to explain the ergogenic potential of creatine ingestion. Additional issues discussed in this review are the fibre-type specificity of muscle creatine metabolism, the identification of responders versus non-responders to creatine intake, and the scientific background concerning potential side effects of creatine supplementation.